Olezarsen Sodium

– Agreement enables olezarsen to reach people living with conditions associated with elevated triglycerides across the world – – Ionis will continue to independently commercialize TRYNGOLZA™ (olezarsen) in the U.S. – CARLSBAD, CA, USA I March 26, 2025 I Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced that it has entered into a license agreement under which Sobi® receives exclusive rights in countries outside the U.S., Canada and China to commercialize olezarsen as a potential treatment for familial chylomicronemia syndrome (FCS) and severely elevated triglycerides. Ionis will continue to independently commercialize olezarsen in the U.S. Olezarsen was approved by the FDA in December 2024 under the tradename TRYNGOLZA™ as an adjunct to diet to reduce triglycerides in adults with FCS – the first and only treatment in the U.S. for this rare, debilitating genetic disease. Olezarsen is currently under review by the European Medicines Agency (EMA) with a potential approval anticipated for the treatment of FCS this year. Sobi will be responsible for future regulatory submissions and commercialization in ex-U.S. geographies except Canada and China. Olezarsen was licensed to Theratechnologies for commercialization in Canada. “We look forward to deepening our long-standing partnership with Sobi and our shared commitment to improving the lives of people living with conditions marked by severely elevated triglycerides,” said Brett P. Monia, Ph.D., chief executive officer, Ionis. “This agreement enables us to advance our goal of making olezarsen available to patients globally, while focusing our independent commercialization efforts in the U.S. With anticipated data from our robust sHTG Phase 3 program in 2025, we are enthusiastic about the potential for olezarsen to also address the significant medical need in this more prevalent patient population in addition to FCS.” Sobi® (STO: SOBI) brings deep commercialization expertise for both rare and more prevalent conditions, with operations in more than 30 countries, and is committed to bringing olezarsen to as many global patients as possible. As Ionis’ current European commercialization partner for Waylivra® (volanesorsen), which is the only medicine approved for FCS in Europe, Sobi will leverage existing market expertise and distribution channels to enable an effective olezarsen launch in FCS and future potential expansion to a broader population with severely elevated triglycerides, assuming approval. Under the agreement, Ionis receives an upfront payment, additional payments based on achievement of milestones and a tiered royalty of up to mid-20% range on annual net sales. “We are thrilled to continue our collaboration with Ionis and bring this potential new medicine to patients if approved,” said Guido Oelkers, chief executive officer, Sobi. “This will enable us to further leverage our combined strengths and to continue to deliver our commitment to provide innovative medicines that transform the lives of people with rare and debilitating diseases.” In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in three Phase 3 clinical trials – CORE , CORE2 and ESSENCE . Data from ESSENCE are expected mid-2025 and data from CORE and CORE2 are expected in the second half of 2025. About Familial Chylomicronemia Syndrome (FCS) FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL). Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides. FCS is estimated to impact up to approximately 3,000 people in the U.S. People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain. People living with FCS are sometimes unable to work, adding to the burden of disease. About Severe Hypertriglyceridemia (sHTG) sHTG is a disease categorized by triglyceride levels of 500 mg/dL and above. It develops due to primary (genetic) and secondary causes including diet and lifestyle, other medical conditions and certain medications. More than three million people are currently estimated to live with sHTG in the U.S. People living with sHTG are at risk of potentially life-threatening acute pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Olezarsen has not been reviewed or approved for the treatment of severe hypertriglyceridemia (sHTG) by any regulatory authority. About TRYNGOLZA™ (olezarsen) TRYNGOLZA™ (olezarsen) was approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). TRYNGOLZA is an RNA-targeted medicine designed to lower the body’s production of apoC-III, a protein produced in the liver that is a key regulator of triglyceride metabolism. It is the only treatment currently indicated in the U.S. for FCS, a potentially life-threatening disease. For more information about TRYNGOLZA, visit TRYNGOLZA.com . IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to TRYNGOLZA or any of the excipients in TRYNGOLZA. Hypersensitivity reactions requiring medical treatment have occurred. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills and myalgias) have been reported in patients treated with TRYNGOLZA. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur. ADVERSE REACTIONS The most common adverse reactions (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count and arthralgia. Please see full Prescribing Information for TRYNGOLZA. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has six marketed medicines and a leading pipeline in neurology, cardiology, and select areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram . SOURCE: Ionis Pharmaceuticals

Ionis Pharmaceuticals previously investigated sapablursen in another blood disorder called beta thalassemia.\n Japan\'s Ono Pharmaceutical is handing over $280 million upfront to acquire Ionis Pharmaceuticals’ phase 2-stage antisense oligonucleotide for a rare type of blood cancer.The RNA-targeted medicine, called sapablursen, is designed to reduce the production of a protein called TMPRSS6. The idea is that this increases the expression of hepcidin, which is the key regulator of iron homeostasis, thereby helping treat various blood diseases.Sapablursen is currently in a phase 2 trial for polycythemia vera (PV), a rare blood condition characterized by the overproduction of red blood cells. As part of the licensing deal with Ono, Ionis will remain responsible for the midstage study.Beyond that, Ono will become solely responsible for sapablursen’s development, regulatory filings and commercialization, according to a post-market release March 11.In return, Ono is handing over $280 million upfront, with potentially up to $660 million to follow in additional development, regulatory and sales milestones, along with mid-teen royalties on annual net sales.Ionis had previously investigated sapablursen in another blood disorder called beta thalassemia before ending those plans in 2023 after looking at midphase efficacy data and instead focusing on PV.At the time, Ionis CEO Brett Monia, Ph.D., said the company had seen “quite remarkable” target engagement in phase 1 plus “very significant elevations in hepcidin levels.” However, “in beta-thalassemia intermedia, we didn\'t see those changes,” the CEO explained back in 2023.In yesterday’s release, Monia said the company was “pleased to entrust sapablursen to Ono, whose unique capabilities will help maximize its value by ensuring broad access for people living with PV.” Ionis recently became a commercial-stage company as a result of the approval of Tryngolza to treat the rare genetic disorder familial chylomicronemia syndrome in December.“Ionis remains committed to advancing the wholly owned medicines we choose to commercialize ourselves, which includes our first independent launch currently underway and three additional anticipated launches in the next three years,” Monia added. “Streamlining our Ionis-owned portfolio provides financial flexibility, supporting our commitment to invest in and focus on our near and mid-term commercial opportunities and generate substantial revenue growth.”Meanwhile, Ono—which codeveloped blockbuster cancer immunotherapy Opdivo with Bristol Myers Squibb—is active in the oncology space, where it is working on a slate of antibodies as well as some multispecific molecules and cell therapies. Last year, the biotech got in on the antibody-drug conjugate action via a $700 million biobucks deal with LigaChem Biosciences.The partnership with Ionis “aligns with our strategy to strengthen our pipeline in hematology,” said Ono President and Chief Operating Officer Toichi Takino, who added that the company “expects sapablursen to become a new treatment option for PV patients worldwide.”The deal comes a week after Takeda and Protagonist Therapeutics posted a phase 3 win for their own PV prospect, an injectable hepcidin mimetic called rusfertide.“While rusfertide is likely to be first to market in the hepcidin-boosting drug class, we see sapablursen as a potential improvement in treatment regimen that will be attractive to patients and healthcare providers,“ William Blair analysts said in a March 12 note, adding that Ono\'s deal with Ionis was “positive for both sides.“